Anti‐Müllerian hormone signaling is influenced by Follistatin 288, but not 14 other transforming growth factor beta superfamily regulators

The hypothesis that, in contrast to other transforming growth factor‐beta (TGFβ) superfamily ligands, the dose–response curve of Anti‐Müllerian hormone (AMH) is unmodulated was tested by examining whether known TGFB superfamily modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM. Follistatins (FS) produced concentration‐dependent increases in AMHC‐ and AMHN,C‐initiated reporter activity, with FS288 being more potent than FS315; however, the maximum bioactivity of AMH was not altered by either follistatin. Thirteen other TGFβ regulators (Chordin, Chordin‐like 1, Chordin‐like 2, Differential screening‐selected gene aberrative in neuroblastoma [DAN], Decorin, Endoglin, Follistatin‐like 1, Follistatin‐like 3, Follistatin‐like 4, Noggin, α2 macroglobulin, TGFβ receptor 3, Von Willebrand factor C domain‐containing 2) had little or no effect. Surface plasmon resonance analysis showed no significant association between FS288 and AMHC, suggesting that FS288 indirectly regulates AMH signaling. Activin A, a direct target of FS288, did not itself induce reporter activity in P19 cells, but did prevent the FS288‐induced increase in AMH signaling. Hence, local concentrations of FS288 and Activin A may influence the response of some cell types to AMH.